Preventing Metabolic Side Effects of Thiazide Diuretics With KMgCitrate

CTD- induced metabolic side effects were though to be dependent on hypokalemia, but
subsequent studies suggested that CTD - induced side effects were independent from
hypokalemia. On the other hand, magnesium depletion has been linked to increased
Renin-Angiotensin- Aldosterone (RAA) system, the development of metabolic syndrome and
insulin resistance with magnesium supplementation ameliorating these effects.

Participants will participate in a double-blinded, parallel design study. After baseline
evaluation participants will take Chlorthalidone (CTD) alone for 2-3 weeks. They will then be
randomized to two equal groups to take KMgCit powder or Potassium Chloride (KCl) powder along
with CTD for 4 months.

We speculate that Mg depletion is responsible for hepatic fat deposition, which then produces
insulin resistance. Co-administration of KMgCit powder would avert magnesium (Mg) depletion,
block hepatic fat deposition by restoring normal Mg status and direct intestinal binding of
fat, thereby ameliorating insulin resistance. To test this hypothesis, we shall quantitate
muscle Mg status and hepatic fat content by magnetic resonance spectroscopy (MRS) before and
after KMgCit. Change in fasting glucose, insulin resistance, serum potassium, FGF23, and
aldosterone will be compared between KCL and KMgCit groups after 4 months.

Inclusion Criteria:

• Treated or untreated stage I hypertension

Exclusion Criteria:

- Diabetes mellitus,

- Renal impairment (serum creatinine > 1.4 mg/dL),

- Any heart diseases such as congestive heart failure, sustained arrhythmia, or coronary
heart disease,

- Chronic regular NSAID use,

- Allergy to thiazide diuretics,

- Gastro-esophageal reflux disease (GERD) requiring treatment with acid reducing agents
or antacid more than once a week,

- Esophageal-gastric ulcer or history of gastrointestinal bleeding,

- Chronic diarrhea, vomiting,

- Excessive sweating,

- Unprovoked hypokalemia (serum K < 3.5 mmol/L) or hyperkalemia (serum K > 5.3 mmol/L),

- Abnormal liver function test (Aspartate transaminase (AST) or Alanine transaminase
(ALT) above upper limit of normal range),

- Subjects on any potassium supplement on a regular basis for any reason, such as
patients with primary aldosteronism,

- Pregnancy,

- History of major depression, bipolar disorder, or schizophrenia,

- History of substance abuse,

- Gout,

- Metabolic alkalosis, with serum bicarbonate > 32 meq/L,

- Severe dietary salt restriction, less than1/2 spoonful or 50 meq sodium/day.

- Claustrophobia

- Metal implants